title: Comprehensive analysis of human endogenous retrovirus group HERV-W locus transcription in multiple sclerosis brain lesions by high-throughput amplicon sequencing.
abstract: Human endogenous retroviruses (HERVs) of the HERV-W group comprise hundreds of loci in the human genome. Deregulated HERV-W expression and HERV-W locus ERVWE1-encoded Syncytin-1 protein have been implicated in the pathogenesis of multiple sclerosis (MS). However, the actual transcription of HERV-W loci in the MS context has not been comprehensively analyzed. We investigated transcription of HERV-W in MS brain lesions and white matter brain tissue from healthy controls by employing next-generation amplicon sequencing of HERV-W env-specific reverse transcriptase (RT) PCR products, thus revealing transcribed HERV-W loci and the relative transcript levels of those loci. We identified more than 100 HERV-W loci that were transcribed in the human brain, with a limited number of loci being predominantly transcribed. Importantly, relative transcript levels of HERV-W loci were very similar between MS and healthy brain tissue samples, refuting deregulated transcription of HERV-W env in MS brain lesions, including the high-level-transcribed ERVWE1 locus encoding Syncytin-1. Quantitative RT-PCR likewise did not reveal differences in MS regarding HERV-W env general transcript or ERVWE1- and ERVWE2-specific transcript levels. However, we obtained evidence for interindividual differences in HERV-W transcript levels. Reporter gene assays indicated promoter activity of many HERV-W long terminal repeats (LTRs), including structurally incomplete LTRs. Our comprehensive analysis of HERV-W transcription in the human brain thus provides important information on the biology of HERV-W in MS lesions and normal human brain, implications for study design, and mechanisms by which HERV-W may (or may not) be involved in MS.
authors.affiliation: Institute of Human Genetics, Center of Human and Molecular Biology, Medical Faculty, University of Saarland, Homburg/Saar, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Schmitt
authors.forename: Christin
authors.initials: C
authors.lastname: Richter
authors.forename: Christina
authors.initials: C
authors.lastname: Backes
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
authors.forename: Jens
authors.initials: J
authors.lastname: Mayer
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000821:virology*; D016022:Case-Control Studies; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000302:isolation & purification; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000235:genetics* / Q000821:virology*; D014158:Transcription, Genetic